PROJECTSUMMARY/ABSTRACT Research:TheNationalLungScreeningTrial(NLST)demonstrateda20%reductioninmortalitywiththeuse ofannualCTscreeningbutwithsignificantmorbidityduetoproceduresperformedforevaluationofthe94%of nodulesthatwerenotcancerous.Thegoalofthisproposalistoimprovethespecificityfordistinguishingwhich of these ?indeterminate? nodules is lung cancer by using quantitative features associated with emphysema availablefromasingleCTscan.Ourpreliminarydataindicatethatmoderatecentrilobularemphysema(MCE), anditsassociatedvascularfeatures,provideanicheforthegrowthofnascentlung.Aninnovativeapproachof this proposal is to use features of MCE in the sphere of lung around a nodule to improve specificity for detecting cancer. However, increasing specificity results in decreasing sensitivity. In the case of lung cancer screening more ?missed? cancers may increase lung cancer deaths. To understand the effect of decreasing sensitivity on mortality we will use the novel UVM Lung Cancer Model, which accurately recapitulates lung cancerdeathandCTscreeningrates,toidentifyanoptimalsetofbiomarkersforidentifyingcanceramongthe manyscreendetectednodules. Candidate: Dr. Kinsey?s clinical practice is in Interventional Pulmonary, a specialty that focuses on dealing with the problem of indeterminate nodules. He has applied his MPH epidemiology and biostatistical training, coupledwithexperienceinquantitativeCTimaging,tobegintoaddresstheproblemofindeterminatenodules intheCOPDGenedatasetandasthePrincipalInvestigatoroftheUVMMolecular,Epigenetic,andRadiologic Biomarkers for Thoracic Cancers (MEROPTIC) study. However, he needs further training in the process of developingCTfeaturesasimagingbiomarkersandincomputermodeling,whichwillallowhimtounderstand the effect of deployment of these biomarkers on lung cancer mortality. To address these critical gaps in knowledge his primary mentor, Dr. Jason Bates, has designed a program of didactic training and supervised researchthatwillpropelDr.Kinseytoanindependentinvestigatorinthefieldoflungcancerdiagnosis. Environment:Dr.Kinsey?sprimarymentor,Dr.Bates,isinternationallyrecognizedforhisworkinpulmonary physiology and computer modeling and has a proven track record of training investigators and physician scientists. The co-mentor, Dr. George Washko, is an expert in quantitative imaging analysis and has an established mentoring relationship with Dr. Kinsey. A scientific advisory committee with established expertise in radiology, biostatistics, lung cancer, and biomarker development complements this outstanding mentoring team. Dr. Kinsey is further supported by a network of individuals and resources, under the auspices of the VermontLungCenterandUniversityofVermontCancerCenter,thatiscommittedtothedevelopmentofjunior investigators.